Overcoming Paradoxical Kinase Priming by a Novel MNK1 Inhibitor.

Targeting the kinases MNK1 and MNK2 has emerged as a valuable strategy in oncology. However, most of the advanced inhibitors are acting in an adenosine triphosphate (ATP)-competitive mode, precluding the evaluation of different binding modes in preclinical settings. Using rational design, we identified and validated the 4,6-diaryl-pyrazolo[3,4-]pyridin-3-amine scaffold as the core for MNK inhibitors.

Publisher Correction: ITGB3-mediated uptake of small extracellular vesicles facilitates intercellular communication in breast cancer cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

ITGB3-mediated uptake of small extracellular vesicles facilitates intercellular communication in breast cancer cells.

Metastasis, the spread of malignant cells from a primary tumour to distant sites, causes 90% of cancer-related deaths. The integrin ITGB3 has been previously described to play an essential role in breast cancer metastasis, but the precise mechanisms remain undefined. We have now uncovered essential and thus far unknown roles of ITGB3 in vesicle uptake.

The role of clonal communication and heterogeneity in breast cancer.

Background: Cancer is a rapidly evolving, multifactorial disease that accumulates numerous genetic and epigenetic alterations. This results in molecular and phenotypic heterogeneity within the tumor, the complexity of which is further amplified through specific interactions between cancer cells. We aimed to dissect the molecular mechanisms underlying the cooperation between different clones.